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Dipeptidyl peptidase 8/9‐like activity in human leukocytes
Author(s) -
Maes MarieBerthe,
Dubois Véronique,
Brandt Inger,
Lambeir AnneMarie,
Van der Veken Pieter,
Augustyns Koen,
Cheng Jonathan D.,
Chen Xin,
Scharpé Simon,
De Meester Ingrid
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0906546
Subject(s) - dipeptidyl peptidase , jurkat cells , biology , isoindoline , dipeptidyl peptidase 4 , cytosol , enzyme , u937 cell , cell fractionation , biochemistry , recombinant dna , protease inhibitor (pharmacology) , protease , microbiology and biotechnology , immunology , t cell , endocrinology , chemistry , apoptosis , diabetes mellitus , virus , immune system , organic chemistry , gene , antiretroviral therapy , type 2 diabetes , viral load
The proline‐specific dipeptidyl peptidases (DPPs) are emerging as a protease family with important roles in the regulation of signaling by peptide hormones. Inhibitors of DPPs have an intriguing, therapeutic potential, with clinical efficacy seen in patients with diabetes. Until now, only recombinant forms of DPP8 and DPP9 have been characterized. Their enzymatic activities have not been demonstrated in or purified from any natural source. Using several selective DPP inhibitors, we show that DPP activity, attributable to DPP8/9 is present in human PBMC. All leukocyte types tested (lymphocytes, monocytes, Jurkat, and U937 cells) were shown to contain similar DPP8/9‐specific activities, and DPPII‐ and DPPIV‐specific activities varied considerably. The results were confirmed by DPPIV/CD26 immunocapture experiments. Subcellular fractionation localized the preponderance of DPP8/9 activity to the cytosol and DPPIV in the membrane fractions. Using Jurkat cell cytosol as a source, a 30‐fold, enriched DPP preparation was obtained, which had enzymatic characteristics closely related to the ones of DPP8 and/or ‐9, including inhibition by allo ‐Ile‐isoindoline and affinity for immobilized Lys‐isoindoline.